Antineutrophil cytoplasmic antibodies in patients treated with methimazole: a prospective Brazilian study / Anticorpos anticitoplasma de neutrófilos em pacientes tratados com metimazol: um estudo prospectivo brasileiro

Abstract Introduction: The side effects of antithyroid drugs are well known. Antineutrophil cytoplasmic antibody-associated vasculitis is a severe adverse reaction. Most studies evaluating antineutrophil cytoplasmic antibodies related to antithyroid drugs have been carried out with patients treated with propylthiouracil, but less information is available for methimazole. Furthermore, most studies that investigated antineutrophil cytoplasmic antibodies related to antithyroid drugs were conducted on Asian populations. Objective: To evaluate the frequency of antineutrophil cytoplasmic antibodies and antineutrophil cytoplasmic antibodies-positive vasculitis in an adult population of Brazilian patients treated with methimazole. Methods: This was a prospective study. We evaluated patients ≥18 years with Graves' disease who have been using methimazole for at least 6 months (Group A, n = 36); with Grave's disease who had been previously treated with methimazole but no longer used this medication for at least 6 months (Group B, n = 33), and with nodular disease who have been using methimazole for at least 6 months (Group C, n = 13). Results: ANCA were detected in 17 patients (20.7%). Four patients (4.9%) had a strong antineutrophil cytoplasmic antibodies-positive test. The frequency of antineutrophil cytoplasmic antibodies was similar in the groups. When Groups A and B were pooled and compared to Group C to evaluate the influence of Grave's disease, and when Groups A and C were pooled and compared to Group B to evaluate the influence of methimazole discontinuation, no difference was found in the frequency of antineutrophil cytoplasmic antibodies. No difference was observed in sex, age, etiology of hyperthyroidism, anti-TSH receptor antibodies, dose or time of methimazole use between patients with versus without antineutrophil cytoplasmic antibodies. The titers of these antibodies were not correlated with the dose or time of methimazole use. None of the antineutrophil cytoplasmic antibodies-positive patient had clinical event that could potentially result from vasculitis. Conclusion: This clinical study of a Brazilian population shows a considerable frequency of antineutrophil cytoplasmic antibodies in patients treated with methimazole but the clinical repercussion of these findings remains undefined.

Resumo Introdução: Os efeitos adversos de drogas antitireoidianas são conhecidos. Vasculite associada a anticorpos anticitoplasma de neutrófilos é uma reação adversa grave. A maioria dos estudos que avaliam anticorpos anticitoplasma de neutrófilos relacionado a drogas antitireoidianas envolveu pacientes tratados com propiltiouracil, entretanto menos informação se encontra disponível para o metimazol. Além disso, a maioria dos estudos que investigaram anticorpos anticitoplasma de neutrófilos relacionado a drogas antitireoidianas foi conduzida em populações asiáticas. Objetivo: Avaliar a frequência de anticorpos anticitoplasma de neutrófilos e vasculite anticorpos anticitoplasma de neutrófilos-positivo em uma população adulta de pacientes brasileiros tratados com metimazol. Método: Este foi um estudo prospectivo. Avaliamos pacientes ≥ 18 anos com doença de Graves com o uso de metimazol há pelo menos seis meses (Grupo A, n = 36); com doença de Graves previamente tratados com metimazol, mas que não usaram esse medicamento por pelo menos seis meses (Grupo B, n = 33) e com doença nodular em uso de metimazol há pelo menos seis meses (Grupo C, n = 13). Resultado: Anticorpos anticitoplasma de neutrófilos foram detectados em 17 pacientes (20,7%). Quatro pacientes (4,9%) tinham anticorpos anticitoplasma de neutrófilos fortemente positivos. A frequência de anticorpos anticitoplasma de neutrófilos foi semelhante nos grupos. Quando os Grupos A e B foram somados e comparados ao Grupo C para avaliar a influência da doença de Graves, e quando os Grupos A e C foram somados e comparados ao Grupo B para avaliar a influência da interrupção do metimazol, não foi encontrada diferença na frequência de anticorpos anticitoplasma de neutrófilos. Não houve diferença em relação a sexo, idade, etiologia do hipertireoidismo, anticorpos antirreceptor de TSH, dose ou tempo de uso de metimazol entre pacientes com e sem anticorpos anticitoplasma de neutrófilos. Os títulos desses anticorpos não se correlacionaram com dose ou tempo de uso de metimazol. Nenhum paciente anticorpos anticitoplasma de neutrófilos-positivo apresentou evento clínico resultante de vasculite. Conclusão: Este estudo clínico de uma população brasileira apresenta frequência considerável de anticorpos anticitoplasma de neutrófilos em pacientes tratados com metimazol, mas a repercussão clínica desse achado permanece indefinida.

Neutropenia febril asociada a la ingesta de metimazol: reporte de caso / Febrile neutropenia associated with methimazole ingestion: case report

La neutropenia se define como un recuento absoluto de neutrófilos menor a 1500 células /µL. Se debe a la disminución en la producción de granulocitos o al aumento en su destrucción, ya sea a nivel medular o periférico. Según la clasificación de la Organización Mundial de la Salud (OMS) los grados de neutropenia van de 0 a IV, de acuerdo a la magnitud de la disminución del recuento de neutrófilos. El grado IV es el de mayor riesgo y corresponde a recuentos por debajo de 500 células/µL. El impacto en la morbimortalidad asociada a la neutropenia no está vinculado con la disminución directa del recuento celular, sino con los procesos infecciosos asociados a los que son propensos los pacientes que la presentan. Existen diversas condiciones por las que se puede desarrollar neutropenia, entre las que se encuentran las infecciones, las malignidades y los fármacos. Estos últimos pueden generar eventos adversos por mecanismos dosis dependiente, como en el caso de la quimioterapia citotóxica o por una reacción idiosincrática. Se presenta el caso de una paciente femenina de 37 años de edad, con antecedentes de tirotoxicosis, tratada con propanolol y metimazol durante cuatro semanas, quien además de manifestaciones tóxicas, presentó neutropenia febril muy grave, que mejoró luego de suspensión del antitiroideo. Se pretende resaltar la asociación de neutropenia febril como complicación de uso de tionamidas y la importancia del seguimiento con exámenes de laboratorios para un diagnóstico oportuno(AU)

Neutropenia is defined as an absolute neutrophil count less than 1500 cells / μL. It is due to the decrease in the production of granulocytes or increase in their destruction, either at the medullary or peripheral level. According to the classification of the World Health Organization (WHO) the degrees of neutropenia range from 0 to IV, taking into account the magnitude of the decrease in the neutrophil count. Grade IV is the highest risk and corresponds to counts below 500 cells /μL. The impact on morbidity and mortality associated with neutropenia is not linked to the direct reduction of the cell count, but to the associated infectious processes to which patients who present it are prone. There are several conditions under which neutropenia can develop, including infections, malignancies and drugs. The latter can generate adverse effects by dose-dependent mechanisms, as in the case of cytotoxic chemotherapy or an idiosyncratic reaction. Next, the case of a female patient of thirty-seven years of age, with a history of thyrotoxicosis, treated with propanolol and methimazole for four weeks, who in addition to toxic manifestations, presents very severe febrile neutropenia that improves after suspension of the antithyroid. We aim to highlight the association of febrile neutropenia as a complication of thionamide use and the importance of follow-up with laboratory tests for an opportune diagnosis(AU)

Efectos adversos severos del Metimazol. Comunicación de dos casos y revisión de la literatura / Severe adverse effects of Methimazole. Communication of two cases and review of the literature

Los fármacos antitiroideos constituyen uno de los pilares del tratamiento del hipertiroidismo. En nuestro país solo se encuentra disponible el metimazol. Estas drogas han sido asociadas a múltiples reacciones adversas, la mayoría leves. Efectos adversos infrecuentes pero potencialmente letales como la agranulocitosis, hepatitis y el síndrome de artritis por antitiroideos, obligan a suspender el tratamiento. Comunicamos dos casos de complicaciones infrecuentes del tratamiento con metimazol.

Antithyroid drugs are one of the cornerstones in the management of hyperthyroidism. In our country, only methimazole is available. These drugs have been related to a variety of adverse reactions, most of them minor. Infrequent but potentially lethal side effects such as agranulocytosis, hepatitis and the antithyroid arthritis syndrome, demand drug cessation. We report two cases of infrequent complications of methimazole.

Risk of congenital anomalies associated with antithyroid treatment during pregnancy: a meta-analysis

To evaluate the association of either propylthiouracil or methimazole treatment for hyperthyroidism during pregnancy with congenital malformations, relevant studies were identified by searching Medline, PubMed, the Cochrane Library and EMBASE. We intended to include randomized controlled trials, but no such trials were identified. Thus, we included cohort studies and case-control studies in this meta-analysis. A total of 7 studies were included in the meta-analyses. The results revealed an increased risk of birth defects among the group of pregnant women with hyperthyroidism treated with methimazole compared with the control group (odds ratio 1.76, 95% confidence interval 1.47-2.10) or the non-exposed group (odds ratio 1.71, 95% confidence interval 1.39-2.10). A maternal shift between methimazole and propylthiouracil was associated with an increased odds ratio of birth defects (odds ratio 1.88, 95% confidence interval 1.27-2.77). An equal risk of birth defects was observed between the group of pregnant women with hyperthyroidism treated with propylthiouracil and the non-exposed group (odds ratio 1.18, 95% confidence interval 0.97-1.42). There was only a slight trend towards an increased risk of congenital malformations in infants whose mothers were treated with propylthiouracil compared with in infants whose mothers were healthy controls (odds ratio 1.29, 95% confidence interval 1.07-1.55). The children of women receiving methimazole treatment showed an increased risk of adverse fetal outcomes relative to those of mothers receiving propylthiouracil treatment. We found that propylthiouracil was a safer choice for treating pregnant women with hyperthyroidism according to the risk of birth defects but that a shift between methimazole and propylthiouracil failed to provide protection against birth defects. .

Therapeutic Plasmapheresis Enabling Radioactive Iodine Treatment in a Patient with Thyrotoxicosis

Therapeutic plasma exchange (TPE) is one possible treatment for patients resistant to conventional antithyroid drugs or requiring urgent attention for thyrotoxicosis. We report a 35-yr-old man with thyrotoxicosis, ultimately attributed to Graves' disease in whom antithyroid drug used initially was soon discontinued, due to abnormal liver function, and replaced by Lugol's solution. Three weeks later, an escape phenomenon (to Lugol's solution) was apparent, so we performed TPE to control the thyrotoxicosis. Two courses of TPE by a centrifugal type machine resulted in diminished levels of thyroid hormone levels, which then rebounded after another two courses of membrane filtration type TPE. However, the patient could be treated with radioactive iodine therapy without any complications at present.

Ictericia colestásica inducida por metimazol en una paciente con hipertiroidismo / [Methimazole-induced cholestatic jaundice in a hyperthyroid patient].

Hyperthyroidism is one of the most frequent endocrine disorders and its current treatment is based on drugs, surgery and radioactive iodine. Methimazole is the antithyroid drug of choice because of its potency and infrequent side effects, usuaIly mild. This medication is rarely associated with liver toxicity, usually manifested as cholestatic jaundice. Here we report the case of a 33-year-old woman treated at the University Hospital Fundación Santa Fe de Bogota, with hepatotoxicity induced by a methimazole-based treatment for Graves’ disease. The pruritus and jaundice appeared after three weeks of therapy, viral hepatitis markers were negative, hepatobiliary ultrasonography was normal, and an increase of the levels of alkaline phosphatase, total bilirubin and aminotransferases was found The causal diagnosis of methimazole-induced hepatotoxicity was supported by the results of a liver biopsy. According to the CIOMS scale the score was 10, and the causal relationship of the hepatic adverse reaction by methimazole is highly probable. The clinical course was satisfactory when the medication was suspended, with clinical improvement at 5 days, and normalization of liver tests at 5 weeks. We discuss this case from a diagnostic and therapeutic approach.

Acute Pancreatitis Induced by Methimazole Treatment in a 51-Year-Old Korean Man: A Case Report

Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain, two weeks after commencement on MMI for the treatment of Graves' disease. There was no evidence of agranulocytosis, and fever subsided soon after stopping MMI treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain and fever developed again. His symptoms, biochemical, and imaging studies were compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical improvement. This is the first case of MMI-induced acute pancreatitis in Korea. Clinicians should be aware of the rare but possible MMI-induced pancreatitis in patients complaining of fever and abdominal pain.

Acute Pancreatitis Induced by Methimazole Treatment in a 51-Year-Old Korean Man: A Case Report

Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain, two weeks after commencement on MMI for the treatment of Graves' disease. There was no evidence of agranulocytosis, and fever subsided soon after stopping MMI treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain and fever developed again. His symptoms, biochemical, and imaging studies were compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical improvement. This is the first case of MMI-induced acute pancreatitis in Korea. Clinicians should be aware of the rare but possible MMI-induced pancreatitis in patients complaining of fever and abdominal pain.

Agranulocitosis inducida por metimazol en pacientes con enfermedad de Graves / Methimazole-induced agranulocytosis in patients with Graves’ disease

Objetivo: Describir las características clínicas y epidemiológicas de los pacientes con enfermedad de Graves que presentaron agranulocitosis inducida por metimazol. Material y métodos: Estudio retrospectivo, tipo serie de casos. Se revisaron las historias clínicas de todos los pacientes con diagnóstico de agranulocitosis inducida por metimazol, atendidos en el Hospital Nacional Arzobispo Loayza, entre enero 2002 y diciembre 2008. Se buscó asociación entre las variables demográficas y clínicas con la mortalidad y el tiempo de recuperación. Resultados: Treinta (0,60%) pacientes con enfermedad de Graves fueron hospitalizados con el diagnóstico de agranulocitosis inducida por metimazol. La mediana de la edad fue 33,5 años y 86,67% fueron mujeres. Al ingreso, todos los pacientes presentaron fiebre y dolor de garganta. El manejo incluyó aislamiento invertido, suspensión del metimazol, administración de antibióticos y glucocorticoides. Doce (40%) pacientes recibieron GM-CSF. El número de granulocitos se normalizó después de 10,59 días y cuatro (13,33%) pacientes murieron por infecciones bacterianas y sepsis. En todos los casos, el tratamiento definitivo fue yodo radioactivo. No hubo diferencia significativa en la edad, sexo, dosis de metimazol, duración del tratamiento y uso de factor estimulante colonia, entre los pacientes fallecidos y los sobrevivientes. Además, el uso de factor estimulante de colonia no redujo el tiempo de recuperación de la agranulocitosis. Conclusión: La agranulocitosis inducida por metimazol es un evento adverso serio y potencialmente mortal. En este grupo de pacientes, la mortalidad fue elevada y el uso de factor estimulante de colonia no disminuyó el tiempo de recuperación.

Objective: To describe the clinical and epidemiological characteristics of patients with methimazole-induced agranulocytosis. Methods: A retrospective, case series study. We reviewed the medical records of all patients diagnosed with methimazole-induced agranulocytosis treated at Hospital Nacional Arzobispo Loayza between January 2002 and December 2008. We sought association between demographic and clinical variables with mortality and recovery time. Results: Thirty (0.60%) patients with GravesÆ disease were hospitalized with a diagnosis of methimazole-induced agranulocytosis. The median age was 33,5 years and 86,67% were women. On admission, all patients had fever and sore throat. The treatment included isolation, suspension of methimazole, antibiotics and glucocorticoids. Twelve (40%) patients received GM-CSF. The granulocyte count was normalized after 10,59 days and four (13.33%) patients died from bacterial infections and sepsis. In all cases, the final treatment was radioiodine. There was no significant difference in age, sex, methimazole dose, duration of treatment, and use of stimulating factor, among the patients who died and survivors. Furthermore, the use of stimulating factor did not reduce the recovery time from agranulocytosis. Conclusion: Methimazole-induced agranulocytosis is a serious and potentially deadly adverse event. In this group of patients, mortality was high and the use of stimulating factor did not decrease the recovery time.

Cutaneous leukocytoclastic vasculitis in the presence of methimazole therapy / Vasculite leucocitoclástica cutânea na vigência de terapêutica com metimazol

Treatment with antithyroid drugs may be accompanied by side effects. We present a patient diagnosed with Grave's Disease who developed extensive vasculitis in the lower limbs during methimazole use. After suspension of the methimazole and the introduction of prednisone in immunesupressor doses the cutaneous lesions started to involute.

A terapêutica com drogas antitireoidianas pode ser acompanhada de efeitos colaterais. Apresentamos um caso de paciente com diagnóstico de Doença de Graves que na vigência da terapêutica com metimazol desenvolveu um quadro extenso de vasculite de membros inferiores. A partir da suspensão do metimazol e da introdução de prednisona em doses imunossupressoras as lesões cutâneas entraram em involução.

Postinfectious Guillain-Barre syndrome in a patient with methimazole-induced agranulocytosis

Both Graves disease and Guillain-Barre syndrome (GBS) are autoimmune disorders caused by impaired self-tolerance mechanisms and triggered by interactions between genetic and environmental factors. GBS in patients who suffer from other autoimmune diseases is rarely reported, and the development of postinfectious GBS in a patient with Graves disease has not been previously reported in the literature. Herein, we report a patient with Graves disease who developed postinfectious GBS during a course of methimazole-induced agranulocytosis.

Aspergilosis pulmonar secundaria a neutropenia inducida por metimazol: reporte de un caso / Pulmonary aspergillosis due to methimazole-induced neutropenia: a case report

Se reporta el caso de una paciente de 48 años de edad con diagnóstico reciente de enfermedad de Graves, quien acudió a emergencia por presentar fiebre, palpitaciones y dolor faríngeo. Su tratamiento regular incluía metimazol. Al ingreso, los análisis mostraron TSH suprimido, T4 libre elevado y neutropenia. La paciente fue hospitalizada, se administraron antibióticos y factor estimulante de colonia. Después de diez días de tratamiento, la paciente presentó leucocitosis, fiebre y hemoptisis. La tomografía de tórax mostró una cavidad con múltiples nódulos en el lóbulo superior derecho. Los cultivos fueron positivos a Aspergillus fumigatus y Aspergillus flavus. Se inició tratamiento con anfotericina B y luego se cambió a voriconazol, a pesar de lo cual no hubo mejoría del cuadro. La paciente falleció por falla multiorgánica.

A 48-year old woman with a recent diagnosis of Graves’ disease arrived at the emergency room with fever, palpitations, and a sore throat. Her regular treatment included methimazole. On admission, laboratory results showed suppressed TSH, elevated free thyroxine, and neutropenia. She was admitted and started on antibiotics and granulocyte-macrophage colony stimulating factor (gm-csf). After ten days, the patient developed leukocytosis, fever, and hemoptysis. Chest CT scan showed a lung cavity with multiple nodules in the upper right lobe. Cultures from a lung biopsy were positive for Aspergillus Fumigatus and Aspergillus Flavus. Amphotericin B was started but then switched to voriconazole, with both treatments failing to result in clinical improvement. The patient died of multi-organ failure.

Methimazole-Induced Bullous Systemic Lupus Erythematosus: A Case Report

Bullous systemic lupus erythematosus (SLE) is a kind of LE-non-specific bullous skin disease that is rarely induced by a medication. We describe the first case of bullous SLE to develop after administration of methimazole. A 31-yr-old woman presented with generalized erythematous patches, multiple bullae, arthralgia, fever, conjunctivitis, and hemolytic anemia. Biopsy of her bulla showed linear deposition of lgG, lgA, C3, fibrinogen, and C1q at dermo-epidermal junction. She was diagnosed as bullous SLE and treated with prednisolone, dapsone, hydroxychloroquine, and methotrexate. Our experience suggests that SLE should be considered as a differential diagnosis when bullous skin lesions develop in patients being treated for hyperthyroidism.

Vasculitis inducida por metimazol. Reporte de caso / Drug-induced vasculitis by metimazol. A case report

Se reporta el caso de una paciente con enfermedad de Graves, que presentó vasculitis asociada al uso de metimazol. Mujer de 14 años, que acudió a consulta por presentar intolerancia al calor, tremor distal y palpitaciones. El examen físico mostró bocio difuso, y el perfil tiroideo, TSH suprimida y hormonas tiroideas elevadas. Los anticuerpos antiperoxidasa tiroidea fueron positivos. Se inició tratamiento con metimazol y beta bloqueadores. Después de 20 días, la paciente regresó por presentar malestar general, fiebre, poliartralgia, lesiones cutáneas maculopapulares yedema de miembros inferiores. Los anticuerpos antinucleares fueron negativos y los anticuerpos anticitoplasma de los neutrófilos (ANCA), positivos. Se suspendió el metimazol y se inició prednisona. Después de 10 días de tratamiento, las molestias desaparecieron y la paciente recibió I. Las vasculitis asociadas al uso de tionamidas son poco frecuentes, no dependen de la dosis y están asociadas a la presencia de anticuerpos tipo ANCA. Clásicamente, afectan a los vasos pequeños de la piel; sin embargo, también pueden afectar los riñones y pulmones. El cuadro clínico se caracteriza por artralgias y mialgias. En algunos casos puede ocurrir insuficiencia renal de grado variable. En la mayoría de casos, el cuadro remite con la suspensión de la droga; pero, en algunos se requiere el uso de glucocorticoides o inmunosupresores.

A 14-year-old woman presented with recent history of heat intolerance, hand tremor and palpitations. Physical examination showed diffuse thyroid enlargement, and thyroid profile, suppressed TSH and elevated thyroid hormones. Anti-TPO antibodies were positive. Initial treatment included methimazole and beta blockers. After twenty days, patient complained of malaise, fever, polyarthralgia, maculopapular rash, and leg swelling. ANA antibodies were negative; however, ANCA antibodies were positive. Methimazole was stopped and prednisone started. Her clinical evolution was good, and she received I. ANCA associated vasculitis related to thionamides are infrequent. These vasculitis affect small vessels of skin, however they can also affect kidneys and lungs. Arthralgia and myalgia are the classical symptoms. In most patients, symptoms disappear after cessation of drug. In some cases, glucocorticoid or immunosuppressive therapy are also needed.

Mucormicosis en un paciente con agranulocitosis secundaria a metimazol: informe de un caso / Case report of mucormycosis in a patient with secondary methimazole-induced agranulocytosis

La agranulocitosis es una complicación poco frecuente de los medicamentos antitiroideos, se presenta en menos de 0.5% de los pacientes en los primeros meses de tratamiento. Se considera el efecto adverso más grave de estos medicamentos, ya que se puede complicar con infecciones severas con una tasa alta de mortalidad. La mucormicosis es una infección micótica severa observada en huéspedes inmunocomprometidos como pacientes con diabetes, neoplasias hematológicas o con tratamiento inmunosupresor; sin embargo, la asociación de mucormicosis con agranulocitosis por metimazol no se ha reseñado previamente. El objetivo de este informe es analizar el caso de una mujer con bocio tóxico difuso y agranulocitosis asociada a metimazol, quien desarrolló mucormicosis rinopalatina.

Agranulocytosis is a rare side effect of antithyroid drugs, it occurs in less than 0.5% of patients, usually during the first few months of treatment. It is considered to be the most serious adverse effect of these medications since it may be complicated by serious, life-threatening infections. Mucormycosis is a severe mycotic infection that usually develops in immunocompromised hosts, such aspatients with diabetes mellitus, hematologic malignancies or immunosuppressive therapy. The association of mucormycosis with methimazole-induced agranulocytosis has not been previously described. The objective of this case presentation is to analyze the case ofa woman with diffuse toxic goiter and methimazole-induced agranulocytosis who developed rhino-palatal mucormycosis.

Lesões orais da agranulocitose pelo uso de metimazol em pacientes com doença de Graves / Oral lesions of methimazole-induced agranulocytosis in a patient with graves desease

A agranulocitose é uma reação adversa rara atribuída ao uso de medicamentos, caracterizada pela redução acentuada de número de leucócitos. Apresenta manifestações sistêmicas gerais sendo que as lesões iniciais podem ocorrer em cavidade oral e orofaringe. Este artigo relata o caso de uma paciente que desenvolveu um quadro de agranulocitose com lesões bucais devido ao uso de Metimazol, droga geralmente prescrita no tratamento do hiperparatireoidismo, o objetivo deste relato é alertar o cirurgião-dentista para a identificação precoce das lesões da agranulocitose, bem como reforçar a importância da anamnese na rotina diária.

The agranulocytosis is a rare adverse reation attributed to the use of some therapeutic drugs, characterized by a decrease of leukocytes counts. It presents systemic manifestations and the first lesions may accur on the oral and oropharynx region. This case report of patient who developed an agranulocytosis with oral lesions induced by the use of Methimazole, a drug usually prescribed to hypertiroidism treatement. The objective of thus report is to alert the dentist to make a prompt identification of the agranulocytosis lesions and to emphasize the importance of anamnesis on the daily routine.

Aplasia cutis congenita after methimazole exposure in utero; a case report and literature review

Aplasia Cutis Congenita [ACC] is a rare disorder with a complicated pattern of| inheritance. Babies are born with the absence of certain layers of skin. It most commonly manifests as a solitary defect on the scalp, but sometimes it may occur as multiple lesions. The affected area is typically covered with a thin, transparent membrane. The skull and/or underlying areas may be visible and be abnormally developed. ACC may be the primary disorder or it may occur in association with other underlying disorders. This article presents a case of ACC in a newborn whose mother was treated with methimazole due to thyrotoxicosis during the first trimester of pregnancy. He was born term with midline scalp defects. This case report is presented to highlight the steps to successful management and review the relevant literature. Management strategies are based on the size and presence of an underlying skull defect. A review of the literature seems to support the hypothesis that methimazole is a potential teratogen. Although the risk of birth defects is low with clinically applied doses of the drug, it cannot be regarded as safe and should therefore be avoided pregnant women. Propylthiouracil should be considered as the first choice drug for hyperthyroid pregnant women until further data on the safety of methimazole are available